O00337 (S28A1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Sodium/nucleoside cotransporter 1

Alternative name(s):
Concentrative nucleoside transporter 1
Short name=CNT 1
Short name=hCNT1
Na(+)/nucleoside cotransporter 1
Sodium-coupled nucleoside transporter 1
Solute carrier family 28 member 1

Gene names

Name:	SLC28A1
Synonyms:	CNT1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	649 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Sodium-dependent and pyrimidine-selective. Exhibits the transport characteristics of the nucleoside transport system cit or N2 subtype (N2/cit) (selective for pyrimidine nucleosides and adenosine). It also transports the antiviral pyrimidine nucleoside analogs 3'-azido-3'-deoxythymidine (AZT) and 2',3'-dideoxycytidine (ddC). It may be involved in the intestinal absorption and renal handling of pyrimidine nucleoside analogs used to treat acquired immunodeficiency syndrome (AIDS). It has the following selective inhibition: adenosine, thymidine, cytidine, uridine >> guanosine, inosine.
Subcellular location	Membrane; Multi-pass membrane protein.
Tissue specificity	Expressed in kidney.
Polymorphism	Three variant forms of isoform 1 (A, B and C) are expressed in the kidney. All three variant forms have similar nucleoside transport activity.
Sequence similarities	Belongs to the concentrative nucleoside transporter (CNT) (TC 2.A.41) family. [View classification]

Ontologies

Keywords
Biological process	Transport
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transmembrane Transmembrane helix
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	nucleobase-containing small molecule metabolic process Traceable author statement. Source: Reactome
Cellular component	integral to plasma membrane Traceable author statement. Source: ProtInc membrane fraction Traceable author statement. Source: ProtInc
Molecular function	nucleoside binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O00337-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: O00337-2)

The sequence of this isoform differs from the canonical sequence as follows:
     155-175: GLALAAFLGLVLWLSLDTSQR → DPRPWSKEGPNQYLPQITWTV
     176-649: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 649	649	Sodium/nucleoside cotransporter 1		PRO_0000070446
Regions
	Transmembrane	85 – 105	21	Helical; Potential
	Transmembrane	109 – 128	20	Helical; Potential
	Transmembrane	153 – 171	19	Helical; Potential
	Transmembrane	177 – 197	21	Helical; Potential
	Transmembrane	205 – 225	21	Helical; Potential
	Transmembrane	261 – 281	21	Helical; Potential
	Transmembrane	361 – 381	21	Helical; Potential
	Transmembrane	428 – 448	21	Helical; Potential
	Transmembrane	532 – 552	21	Helical; Potential
	Transmembrane	572 – 592	21	Helical; Potential
	Compositional bias	609 – 612	4	Poly-Ser
Natural variations
	Alternative sequence	155 – 175	21	GLALA…DTSQR → DPRPWSKEGPNQYLPQITWT V in isoform 2.		VSP_037221
	Alternative sequence	176 – 649	474	Missing in isoform 2.		VSP_037222
	Natural variant	34	1	E → G in A. Ref.1 Ref.2		VAR_009499
	Natural variant	140	1	L → LV in A. Ref.1 Ref.5		VAR_009500
	Natural variant	189	1	V → I in A. Ref.1 Ref.3 Corresponds to variant rs2290272 [ dbSNP | Ensembl ].		VAR_009501
	Natural variant	190	1	A → S. Corresponds to variant rs45523532 [ dbSNP | Ensembl ].		VAR_057194
	Natural variant	237	1	Q → K. Corresponds to variant rs8187758 [ dbSNP | Ensembl ].		VAR_057195
	Natural variant	409	1	N → S in B. Ref.1		VAR_009502
	Natural variant	510	1	R → C. Ref.5 Corresponds to variant rs2242047 [ dbSNP | Ensembl ].		VAR_057196
	Natural variant	521	1	D → N in B and C. Ref.1 Ref.3 Corresponds to variant rs2242046 [ dbSNP | Ensembl ].		VAR_009503
	Natural variant	546	1	S → P. Corresponds to variant rs45584739 [ dbSNP | Ensembl ].		VAR_061802

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 5, 2009. Version 2. Checksum: 42E952443B46B102	FASTA	649	71,584
	10 20 30 40 50 60 MENDPSRRRE SISLTPVAKG LENMGADFLE SLEEGQLPRS DLSPAEIRSS WSEAAPKPFS 70 80 90 100 110 120 RWRNLQPALR ARSFCREHMQ LFRWIGTGLL CTGLSAFLLV ACLLDFQRAL ALFVLTCVVL 130 140 150 160 170 180 TFLGHRLLKR LLGPKLRRFL KPQGHPRLLL WFKRGLALAA FLGLVLWLSL DTSQRPEQLV 190 200 210 220 230 240 SFAGICVFVA LLFACSKHHC AVSWRAVSWG LGLQFVLGLL VIRTEPGFIA FEWLGEQIRI 250 260 270 280 290 300 FLSYTKAGSS FVFGEALVKD VFAFQVLPII VFFSCVISVL YHVGLMQWVI LKIAWLMQVT 310 320 330 340 350 360 MGTTATETLS VAGNIFVSQT EAPLLIRPYL ADMTLSEVHV VMTGGYATIA GSLLGAYISF 370 380 390 400 410 420 GIDATSLIAA SVMAAPCALA LSKLVYPEVE ESKFRREEGV KLTYGDAQNL IEAASTGAAI 430 440 450 460 470 480 SVKVVANIAA NLIAFLAVLD FINAALSWLG DMVDIQGLSF QLICSYILRP VAFLMGVAWE 490 500 510 520 530 540 DCPVVAELLG IKLFLNEFVA YQDLSKYKQR RLAGAEEWVG DRKQWISVRA EVLTTFALCG 550 560 570 580 590 600 FANFSSIGIM LGGLTSMVPQ RKSDFSQIVL RALFTGACVS LVNACMAGIL YMPRGAEVDC 610 620 630 640 MSLLNTTLSS SSFEIYQCCR EAFQSVNPEF SPEALDNCCR FYNHTICAQ
	Isoform 2 [UniParc]. Checksum: 34C7DD93D84F60EE	FASTA	175	20,180
	10 20 30 40 50 60 MENDPSRRRE SISLTPVAKG LENMGADFLE SLEEGQLPRS DLSPAEIRSS WSEAAPKPFS 70 80 90 100 110 120 RWRNLQPALR ARSFCREHMQ LFRWIGTGLL CTGLSAFLLV ACLLDFQRAL ALFVLTCVVL 130 140 150 160 170 TFLGHRLLKR LLGPKLRRFL KPQGHPRLLL WFKRDPRPWS KEGPNQYLPQ ITWTV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and functional expression of cDNAs encoding a human Na+-nucleoside cotransporter (hCNT1)." Ritzel M.W.L., Yao S.Y.M., Huang M.-Y., Elliott J.F., Cass C.E., Young J.D. Am. J. Physiol. 272:C707-C714(1997) [PubMed: 9124315] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS A GLY-34; VAL-140 INS AND ILE-189, VARIANTS B SER-409 AND ASN-521, VARIANT C ASN-521. Tissue: Kidney.
[2]	"Genomic organization and sequence of the gene encoding the human sodium-dependent, pyrimidine-selective nucleoside transporter (CNT1)." Ritzel M.W.L., Ritzel R.G., Cass C.E., Young J.D. Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT A GLY-34.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT A ILE-189, VARIANT B ASN-521, VARIANT C ASN-521. Tissue: Small intestine.
[4]	"Analysis of the DNA sequence and duplication history of human chromosome 15." Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A. , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C. Nature 440:671-675(2006) [PubMed: 16572171] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANTS A VAL-140 INS AND CYS-510. Tissue: Colon.
[6]	"Identification of amino acid residues responsible for the pyrimidine and purine nucleoside specificities of human concentrative Na(+) nucleoside cotransporters hCNT1 and hCNT2." Loewen S.K., Ng A.M.L., Yao S.Y.M., Cass C.E., Baldwin S.A., Young J.D. J. Biol. Chem. 274:24475-24484(1999) [PubMed: 10455109] [Abstract] Cited for: MUTAGENESIS.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U62966 mRNA. Translation: AAB53837.1. U62967 mRNA. Translation: AAB53838.1. U62968 mRNA. Translation: AAB53839.1. AF187978 , AF187969, AF187970, AF187971, AF187972, AF187973, AF187974, AF187975, AF187976, AF187977 Genomic DNA. Translation: AAF15353.1. AK291997 mRNA. Translation: BAF84686.1. AC087468 Genomic DNA. No translation available. AC103741 Genomic DNA. No translation available. BC029788 mRNA. Translation: AAH29788.1. BC039898 mRNA. Translation: AAH39898.1. BC126204 mRNA. Translation: AAI26205.1. BC126206 mRNA. Translation: AAI26207.1.
IPI	IPI00011289. IPI00402760.
RefSeq	NP_004204.3. NM_004213.3. NP_964014.1. NM_201651.1.
UniGene	Hs.459187.
3D structure databases
ProteinModelPortal	O00337.
ModBase	Search...
Protein-protein interaction databases
STRING	O00337.
Protein family/group databases
TCDB	2.A.41.2.3. concentrative nucleoside transporter (CNT) family.
PTM databases
PhosphoSite	O00337.
Proteomic databases
PRIDE	O00337.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000286749; ENSP00000286749; ENSG00000156222. ENST00000394573; ENSP00000378074; ENSG00000156222.
GeneID	9154.
KEGG	hsa:9154.
Organism-specific databases
CTD	9154.
GeneCards	GC15P085427.
HGNC	HGNC:11001. SLC28A1.
MIM	606207. gene.
neXtProt	NX_O00337.
PharmGKB	PA387.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	HBG054073.
InParanoid	O00337.
OMA	TQSELHA.
OrthoDB	EOG4V170B.
PhylomeDB	O00337.
Enzyme and pathway databases
Reactome	REACT_15518. Transmembrane transport of small molecules.
Gene expression databases
ArrayExpress	O00337.
Bgee	O00337.
CleanEx	HS_SLC28A1.
Genevestigator	O00337.
GermOnline	ENSG00000156222. Homo sapiens.
Family and domain databases
InterPro	IPR008276. C_nuclsd_transpt. IPR018270. C_nuclsd_transpt_met_bac. IPR011642. Gate. IPR011657. Nucleos_tra2_C. IPR002668. Nuclsd_transpt2. [Graphical view]
KO	K11536.
PANTHER	PTHR10590. C_nuclsd_transpt. 1 hit.
Pfam	PF07670. Gate. 1 hit. PF07662. Nucleos_tra2_C. 1 hit. PF01773. Nucleos_tra2_N. 1 hit. [Graphical view]
TIGRFAMs	TIGR00804. NupC. 1 hit.
ProtoNet	Search...
Other
SOURCE	Search...

Entry information

Entry name

S28A1_HUMAN

Accession

Primary (citable) accession number: O00337
Secondary accession number(s): A0AV42 , A8K7I2, O00335, O00336, Q5U5S6, Q5U648, Q9UEZ9

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	May 5, 2009
Last modified:	January 25, 2012
This is version 100 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.